Assembling a plug-and-play production line for combinatorial biosynthesis of aromatic polyketides in Escherichia coli
Fig 2
Schematic representation of aromatic polyketide biosynthesis.
(a) Expected octaketide shunt metabolites after each biosynthetic step are designated by grey dotted line. Biosynthetic steps are confined to individual grey boxes that proceed in the order of biosynthesis. Circular arrows within each box represent the ability to functionally substitute biosynthetic enzymes for homologues. (b) Examples of plausible biosynthetic pathway perturbations: b1, the exchange of an octaketide producing PKS heterodimer with a decaketide producer (XU exchange); b2, compound maturation despite loss of KR (TU modification); and b3, alteration of polyketide starter unit by exchanging PU enzyme constituents as well as functional exchange of an aromatase/cyclase and loss of supplementary enzymes (PU and TU exchange). Supplementary enzymes can be variable in function. (c) Structures of AQ256 (1) and its dianthrone (13). ACP, acyl carrier protein; Aro/Cyc, aromatase/cyclase; CLF, chain length factor; DMAC, 3,8-dihydroxy-methylanthraquinone carboxylic acid; KS, ketosynthase; PKS, polyketide synthase; PU, priming unit; TU, tailoring unit; XU, extension unit.